74 - Opening New Vistas in Basic and Preclinical Addiction Research

Abstract

This is a personal perspective on some of the major achievements in addiction research, and especially an attempt to point out some of the most important future challenges in basic and preclinical research in this field. Given that addictive behavior is the result of a very complex drug × gene × environment interaction, which has to be seen even in a lifespan perspective, new genetic approaches will be discussed. In particular, convergent translational genomics approaches are proposed to integrate genomics information from animal models (e.g., by means of microarray analysis) with genetic information from alcoholics or drug addicts (e.g., from genome-wide association studies). This novel tool will help to enhance the explanatory power of genetic findings in addiction research and will be essential to define the genetic profiles that drive the vulnerability to develop addictive behavior. Next the interaction of a drug with primary targets (e.g., receptors) within the brain is discussed. In this context the concept of agonist-directed trafficking of receptor stimulus is introduced for a future key to understand the consequences of drug-receptor interactions and subsequent signaling transduction. In addition, new concepts are discussed with regard to drug-induced synaptic plasticity. Alterations on the synaptic level can modulate neuronal network activity, which can be studied by means of multielectrode recording or ultra-high-field imaging in small rodents. A systems biology approach will then be helpful to integrate data sets obtained on the genetic, molecular, synaptic, and neuronal network level in order to understand addictive behavior. The basic knowledge that derives from such a systems biology approach will be of utmost importance for the improvement of the treatment situation. One appealing future approach to treat alcoholics, smokers, and illicit drug users may be the disruption of reconsolidation of alcohol- or drug-related memories.